Prostaglandins and the derivatives thereof have various biological actions, such as a vasodilating action, a prophlogistic action, an inhibitory action of blood platelet aggregation, a uterine muscle contraction action, an intestine contraction action and a lowering action of intraocular pressure, and can be used in the preparation of medicaments for treatment or prevention of myocardial infarction, angina pectoris, arteriosclerosis, hypertension, or duodenal ulcer, which are valuable for human as well as veterinary applications.
For the last few decades, many academic researchers and industrial organizations have made tremendous efforts in exploring various key intermediates as well as innovative processes for efficient and cost-saving synthesis of Prostaglandins (Collines, P. W. et. al., 1993, Chem. Rev. 93, 1533).
Lolja, D., et al. reported that Cyclopentenones of Formula (R)-1,
wherein R1 is an unsubstituted straight and saturated alkyl, are potential intermediates in the synthesis of Prostaglandins (Lolja, D., et al., Zh. Org. Khim 1985, 21(4), 782). As depicted in Scheme 1 shown below, Beraldi, P. G., et al. converted Cyclopentenone of Formula (R)-1, wherein R1 is methyl, using a nitromethane conjugate addition method, to Corey aldehyde of Formula II, which is an advanced key intermediate in the synthesis of Prostaglandins (Beraldi, P. G., et al., 1987, Tetrahedron, 43, 4669).
Beraldi, P. G., et al. employed a method, as shown below in Scheme 2, for preparing the optically active cyclopentenone of (R)-1, wherein R1 is methyl, in which a diastereomeric oximes is formed by reacting the racemic mixture with a chiral agent (R)-2-aminoxy-4-methylvaleric acid and the desired form of Formula (R)-1 is isolated and obtained from a column separation.

Unfortunately, the two isomers in the diastereomeric oximes produced in the Beraldi's method have structures and properties similar to each other and therefore it is extremely difficult to separate them from each other to obtain the desired product with the desired optical purity using a column chromatography. Moreover, about a half of the compounds that existed as the unwanted isomer is wasted. It seemed that Beraldi's method is not quite economical due to aforementioned reasons.
Alternatively, Veinberga, I. et. al. utilized various enzymatic methods including enzymatic hydrolysis (Latv. Kim. Z. (1-2), 122, 1995 and Latv. Kim. Z. (1-2), 116, 1995) and a two-step enzymatic reaction (Latv. Kim. Z. (1), 103, 1992) to obtain an optically active cyclopentenone of Formula (R)-1 wherein R1 is exclusively methyl. Unfortunately, none of these enzymatic reactions or biocatalysts used by Veinberga, I. et. al. exhibits potential optical selectivity toward the substrates. Therefore, the preparation of an optically active cyclopentenone with an optical purity higher than 85% e.e. (enatiomeric excess) is difficult to be achieved.
In another aspect, conjugate addition approach has been employed to build up the stereochemistry of Prostaglandin cyclopentanes. During the process of the conjugation addition, two new chiral centers are formed as depicted in Scheme 3.

In spite that the reaction is in favor of forming the three substituents on the cyclopentane ring respectively in trans orientation due to kinetic equilibrium, the stereoisomers with cis orientation are inevitably formed. The critical concern has been focused on how to remove the stereoisomers left in the conjugated products or how to reduce the stereoisomers generated during the conjugation addition process. In order to facilitate the removal of these stereoisomers, it is anticipated that RI should render the crystallinity of the compounds higher so as to enable easy separation of cis isomers from the conjugated products by crystallization. Alternatively, it is suggested to employ cyclopentenone (R)-1 having bulkier substituents to proceed the reaction in that a bulkier R1 will minimize the generation of the cis isomers. Unfortunately, conventional technology related to cyclopentenone (R)-1 has been confined to R1 being unsubstituted straight and saturated alkyl groups which either are non-bulky or have poor crystallinity. Studies concerning R1 being bulky alkyl, aryl, or aralkyl groups have never been investigated before.